Association between Gc genotype and susceptibility to TB is dependent on vitamin D status

被引：84

作者：

Martineau, A. R. ^{[1
,2
,3
]}

Leandro, A. C. C. S. ^{[4
]}

Anderson, S. T. ^{[5
]}

Newton, S. M. ^{[5
]}

Wilkinson, K. A. ^{[3
,6
]}

Nicol, M. P. ^{[6
,7
,8
]}

Pienaar, S. M. ^{[9
]}

Skolimowska, K. H. ^{[6
]}

Rocha, M. A. ^{[4
]}

Rolla, V. C. ^{[10
]}

Levin, M. ^{[5
]}

Davidson, R. N. ^{[11
]}

Bremner, S. A. ^{[1
]}

Griffiths, C. J. ^{[1
]}

Eley, B. S. ^{[9
]}

Bonecini-Almeida, M. G. ^{[4
]}

Wilkinson, R. J. ^{[3
,6
]}

机构：

[1] Barts & London Queen Marys Sch Med & Dent, Ctr Hlth Sci, London E1 2AT, England

[2] Univ London Imperial Coll Sci Technol & Med, Wellcome Trust Ctr Res Clin Trop Med, Div Med, London, England

[3] Natl Inst Med Res, Div Mycobacterial Res, Mill Hill, England

[4] Fiocruz MS, Inst Pesquisa Clin Evandro Chagas, Lab Imunol & Imunogenet, BR-21045900 Rio De Janeiro, Brazil

[5] Univ London Imperial Coll Sci Technol & Med, Div Med, Acad Dept Paediat, London, England

[6] Univ Cape Town, Inst Infect Dis & Mol Med, Fac Hlth Sci, ZA-7925 Cape Town, South Africa

[7] Univ Cape Town, Div Med Microbiol, Fac Hlth Sci, ZA-7925 Cape Town, South Africa

[8] Univ Cape Town, Natl Hlth Lab Serv, ZA-7925 Cape Town, South Africa

[9] Univ Cape Town, Sch Child & Adolescent Hlth, Red Cross Childrens Hosp, Paediat Infect Dis Unit, ZA-7925 Cape Town, South Africa

[10] Fiocruz MS, Inst Pesquisa Clin Evandro Chagar, Lab Clin TB & Micobacterias, BR-21045900 Rio De Janeiro, Brazil

[11] Northwick Pk Hosp & Clin Res Ctr, NW London Hosp NHS Trust, TB Clin, Harrow HA1 3UJ, Middx, England

来源：

EUROPEAN RESPIRATORY JOURNAL | 2010年 / 35卷 / 05期

基金：

英国惠康基金;

关键词：

Gc genotype; 25-hydroxyvitamin D; tuberculosis; vitamin D binding protein; D-BINDING PROTEIN; MYCOBACTERIUM-TUBERCULOSIS INFECTION; AFFINITY DIFFERENCES; D DEFICIENCY; PHENOTYPE; METABOLITES; LINKAGE; ALLELE; WOMEN; RISK;

D O I：

10.1183/09031936.00087009

中图分类号：

R56 [呼吸系及胸部疾病];

学科分类号：

摘要：

Group-specific component (Gc) variants of vitamin D binding protein differ in their affinity for vitamin D metabolites that modulate antimycobacterial immunity. We conducted studies to determine whether Gc genotype associates with susceptibility to tuberculosis (TB). The following subjects were recruited into case-control studies: in the UK, 123 adult TB patients and 140 controls, all of Gujarati Asian ethnic origin; in Brazil, 130 adult TB patients and 78 controls; and in South Africa, 281 children with TB and 182 controls. Gc genotypes were determined and their frequency was compared between cases versus controls. Serum 25-hydroxyvitamin D (25(OH) D) concentrations were obtained retrospectively for 139 Gujarati Asians, and case-control analysis was stratified by vitamin D status. Interferon (IFN)-gamma release assays were also performed on 36 Gujarati Asian TB contacts. The Gc2/2 genotype was strongly associated with susceptibility to active TB in Gujarati Asians, compared with Gc1/1 genotype (OR 2.81, 95% CI 1.19-6.66; p=0.009). This association was preserved if serum 25(OH)D was < 20 nmol.L(-1) (p=0.01) but not if serum 25(OH)D was >= 20 nmol.L(-1) (p=0.36). Carriage of the Gc2 allele was associated with increased PPD of tuberculin-stimulated IFN-gamma release in Gujarati Asian TB contacts (p=0.02). No association between Gc genotype and susceptibility to TB was observed in other ethnic groups studied.

引用

页码：1106 / 1112

页数：7

共 28 条

[1] The Gc2 allele of the vitamin D binding protein is associated with a decreased postmenopausal breast cancer risk, independent of the vitamin D status [J].

Abbas, Sascha ;

Linseisen, Jakob ;

Slanger, Tracy ;

Kropp, Silke ;

Mutschelknauss, Elke Jonny ;

Flesch-Janys, Dieter ;

Chang-Claude, Jenny .

CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2008, 17 (06) :1339-1343

[2]

ARNAUD J, 1993, HUM GENET, V92, P183

[3]

BAHR GM, 1989, IMMUNOLOGY, V67, P126

[4]

CLEMENS TL, 1982, LANCET, V1, P74

[5] THE MUTANTS OF THE VITAMIN-D-BINDING PROTEIN - MORE THAN 120 VARIANTS OF THE GC/DBP SYSTEM [J].

CLEVE, H ;

CONSTANS, J .

VOX SANGUINIS, 1988, 54 (04) :215-225

[6] Vitamin D deficiency: time for action [J].

Compston, JE .

BRITISH MEDICAL JOURNAL, 1998, 317 (7171) :1466-1467

[7] AFFINITY DIFFERENCES FOR THE 25-OH-D3 ASSOCIATED WITH THE GENETIC-HETEROGENEITY OF THE VITAMIN-D-BINDING PROTEIN [J].

CONSTANS, J ;

VIAU, M ;

BOUISSOU, C .

FEBS LETTERS, 1980, 111 (01) :107-111

[8] 1α,25-dihydroxyvitamin D3 inhibits matrix metalloproteinases induced by Mycobacterium tuberculosis infection [J].

Coussens, Anna K. ;

Timms, Peter M. ;

Boucher, Barbara J. ;

Venton, Timothy R. ;

Ashcroft, Anthony T. ;

Skolimowska, Keira H. ;

Newton, Sandra M. ;

Wilkinson, Katalin A. ;

Davidson, Robert N. ;

Griffiths, Christopher J. ;

Wilkinson, Robert J. ;

Martineau, Adrian R. .

IMMUNOLOGY, 2009, 127 (04) :539-548

[9] Longitudinal assessment of an ELISPOT test for Mycobacterium tuberculosis infection [J].

Hill, Philip C. ;

Brookes, Roger H. ;

Fox, Annette ;

Jackson-Sillah, Dolly ;

Jeffries, David J. ;

Lugos, Moses D. ;

Donkor, Simon A. ;

Adetifa, Ifedayo M. ;

de Jong, Bouke C. ;

Aiken, Alex M. ;

Adegbola, Richard A. ;

McAdam, Keith P. .

PLOS MEDICINE, 2007, 4 (06) :1061-1070

[10]

HORNE SL, 1990, HUM HERED, V40, P173

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